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The local structure of the filled tetragonal tungsten bronze (TTB) niobate Ba3Nb5−xTixO15 (x = 0, 0.1, 0.7, 1.0), showing a metal-insulator transition with Ti substitution, has been studied by Nb K-edge extended X-ray absorption fine structure (EXAFS) measurements as a function of temperature. The Ti substitution has been found to have a substantial effect on the local structure, that remains largely temperature independent in the studied temperature range of 80–400 K. The Nb-O bonds distribution shows an increased octahedral distortion induced by Ti substitution, while Nb-Ba distances are marginally affected. The Nb-O bonds are stiffer in the Ti substituted samples, which is revealed by the temperature dependent mean square relative displacements (MSRDs). Furthermore, there is an overall increase in the configurational disorder while the system with Nb 4d electrons turns insulating. The results underline a clear relationship between the local structure and the electronic transport properties suggesting that the metal-insulator transition and possible thermoelectric properties of TTB structured niobates can be tuned by disorder.

The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis., info:eu-repo/semantics/published

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD vs placebo, as shown by a lower rate of decline in forced vital capacity (FVC). The adverse event (AE) profile of nintedanib was characterised mainly by gastrointestinal (GI) events, including weight loss.Objectives:Assess FVC decline and AEs in subgroups by weight loss ≤5% vs >5% over 52 weeks in the SENSCIS trial.Methods:Patients with SSc-ILD with first non-Raynaud symptom 5%) over 52 weeks.Results:In the nintedanib (n=288) and placebo (n=288) groups, respectively, 112 (38.9%) and 43 (14.9%) patients had weight loss >5% over 52 weeks. At baseline, patients with weight loss >5% over 52 weeks had a higher mean age (57.0 vs 52.9 years), greater proportion of females (81.3% vs 72.9%), and similar mean BMI (26.5 vs 25.7 kg/m2, respectively) and FVC % predicted (71.0% vs 73.1%, respectively) vs patients with weight loss ≤5%. In the placebo group, the mean (SE) annual rate of decline in FVC was similar between patients who had weight loss ≤5% and >5% over 52 weeks (-92.7 [14.7] mL/year and -96.4 [34.9] mL/year, respectively). The estimated annual rate of decline in FVC was lower in patients treated with nintedanib than placebo, with between-group differences in patients who had weight loss ≤5% and >5% of 49.9 mL/year [95% CI 4.2, 95.6]) and 30.2 mL/year [95% CI -50.5, 110.9]), respectively, with no evidence of heterogeneity between subgroups by weight loss (p=0.68 for interaction). Standardised differences in baseline values of potential confounders were 5%, respectively), nausea (30.1% and 33.9%, respectively) and vomiting (19.3% and 33.3%, respectively). In the nintedanib and placebo groups, respectively, AEs leading to discontinuation of study drug occurred in 17.0% and 8.6% of patients with weight loss ≤5%, and 14.3% and 9.3% of patients with weight loss >5% over 52 weeks.Conclusion:In the SENSCIS trial in patients with SSc-ILD, a greater proportion of patients treated with nintedanib than placebo had weight loss >5% over 52 weeks. The rate of decline in FVC was numerically lower in the nintedanib group than in the placebo group both in patients with weight loss ≤5% and >5% over 52 weeks. AEs leading to discontinuation of nintedanib were not more frequent in patients with weight loss >5% vs ≤5%.References:Disclosure of Interests: :Alain LESCOAT: None declared, Stéphane Jouneau Grant/research support from: AIRB, Boehringer Ingelheim, LVL Medical, Novartis, Roche, Bellorophon Therapeutics, Biogen, Fibrogen, Galecto Biotech, Gilead Sciences, Pharm-Olam, Pliant Therapeutics, Savara Pharmaceuticals/Serendex Pharmaceuticals, Consultant of: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlazoSmithKline, LVL Medical, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Bruno Crestani Grant/research support from: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Novartis, Roche, Sanofi, Consultant of: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Sanofi, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Roche, Sanofi, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Yasuhiro Kondoh Consultant of: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Shionogi, Speakers bureau: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Eisai, KYORIN, Mitsubishi Tanabe Pharma, Novartis, Shionogi, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Nina Patel Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Speakers bureau: Genentech, John Huggins Consultant of: I was a site PI for the SENSCIS trial for Boehringer Ingelheim, Christian Stock Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer

Summary Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise.

Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

The prognosis in idiopathic pulmonary fibrosis (IPF) is poor. No therapy has been shown to prolong survival. The objective of this study was to examine the prognostic significance of dyspnoea in daily living at baseline in IPF using a simple assessment tool. 93 consecutive patients with IPF, who had undergone evaluation at diagnosis, were included. The level of dyspnoea was assessed using the modified Medical Research Council (MRC) scale. The relationship between data at baseline and survival was examined. A univariate Cox proportional-hazard model showed that forced vital capacity % predicted (hazard ratio (HR) 0.965, 95% CI 0.948-0.982; p

Existing mechanical relays have reliability-related issues including unstable contact resistance and limited cycle life. These problems are caused by mechanical fatigue and wearing of the contact surfaces. In the liquid metal micro switch (LiMMS), we employ a liquid-liquid contact to address these issues. The switching operation is achieved by forming a gap in the liquid metal using gas expansion. Our prototype has a microchannel on a glass substrate to hold a tiny amount of mercury, 0.15 mm in width and 0.1 mm in height, and TaN thin-film heaters on a ceramic substrate to expand the operating gas by heating. The substrates are bonded together and the total size of the device is 5/spl times/5/spl times/1.4 mm. We successfully demonstrated 70-m/spl Omega/ on-resistance, 1 ms-switching speed, the ability to handle up to 1 A of dc current and over 1/spl times/10/sup 8/ cycle operation. LiMMS also has good RF performance, better than 1 dB insertion loss, and better than 20 dB isolation up to 18 GHz.

The present study compared the efficacy of cyclophosphamide combined with low-dose prednisolone in the treatment of idiopathic pulmonary fibrosis (IPF) with efficacy in idiopathic fibrosing nonspecific interstitial pneumonia fibrosing (NSIP). A total of 27 patients with IPF and 12 patients with fibrosing NSIP were included in this study. All patients had undergone surgical lung biopsy. The diagnoses were made based on clinical, radiological and pathological findings. All patients were treated with intermittent pulse therapy with methylprednisolone for 4 weeks, followed by cyclophosphamide with low-dose prednisolone. According to pulmonary function tests, four of 27 patients with IPF had improved, 22 remained unchanged, and one had worsened at the completion of pulse therapy. After 1 yr of combination therapy, four of 27 patients had improved, 14 remained unchanged, and nine had worsened. After pulse therapy, four of 12 patients with fibrosing NSIP had improved, and eight remained unchanged. After 1 yr of combination therapy, eight of 12 patients had improved, four remained unchanged, and none had worsened. Median survival of IPF patients was 4.1 yrs, which is significantly worse than that of fibrosing NSIP patients. In conclusion, patients with fibrosing nonspecific interstitial pneumonia had a more favourable response to combination therapy and a better survival than those with idiopathic pulmonary fibrosis.

Mental retardation (MR) occurs in 2–3% of the general population, and more than half of MR patients are categorised as idiopathic—that is, the cause is unknown.1,2 Patients with idiopathic MR are presumed to be affected with certain genetic disorders or undetectable chromosomal abnormalities. MR may also be caused by environmental factors independently or by their interaction with genetic factors. Subtelomeric rearrangements comprise about half of segmental aneusomies,3 and are one of the major causes of MR.4,5 A recent review showed that subtelomeric rearrangements were detected in 131 (5.1%) of 2585 children with MR.1,4–6 Conventional cytogenetic analysis can detect many, but not all, rearrangements, depending on its powers of resolution.4 Other methods, such as fluorescent in situ hybridisation (FISH) using a complete set of subtelomeric probes, multicolour FISH (M-FISH), comparative genomic hybridisation (CGH), spectrum karyotyping, multiple amplifiable probe hybridisation, primed in situ labelling, and genotyping have been designed to detect subtelomeric rearrangements, but none of them is ideal in terms of sensitivity and/or efficiency.4,6 Microarray based CGH is a promising, high throughput method of detecting subtelomeric rearrangements.4 Veltman et al recently reported a microarray CGH system using crude bacterial/plasmid derived artificial chromosome (BAC/PAC) DNA for the analysis of subtelomeric aberrations, and suggested that degenerate oligonucleotide primed (DOP)-PCR products could also be used instead of crude clone DNA, although the performance of DOP-PCR products might be less sensitive.7 We have developed a microarray CGH system to identify rearrangements involving a subtelomeric region, using DOP-PCR that amplifies subtelomeric BAC/PAC DNA. Here we describe details of the method and the results of microarray CGH analyses of five cases of Wolf-Hirschhorn syndrome (WHS) associated with terminal 4p deletions as positive controls, and of 69 patients with idiopathic MR with or without multiple …

The Visual Analogue Scale 8 (VAS8), consisting of eight linear scales, has been developed to measure health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to examine the validity and responsiveness of the VAS8.First, HRQoL was assessed in a cross-sectional study with the VAS8 and the St George's Respiratory Questionnaire (SGRQ) in 46 COPD patients. Relationships between the VAS8 and various physiological parameters were examined. Second, in a longitudinal study, changes in HRQoL scores after pulmonary rehabilitation were evaluated in 29 COPD patients.The total VAS8 scores showed a weak correlation with vital capacity and maximal inspiratory pressure and a moderately strong correlation with 6-min walking distance and dyspnoea rating. The total VAS8 score showed a significant correlation with each SGRQ score. Furthermore, almost every VAS8 and SGRQ score improved significantly after pulmonary rehabilitation. The change in the total VAS8 value showed a strong correlation with that of the SGRQ.The VAS8 is well-suited to assess HRQoL in COPD patients. Visual analogue scales are generally useful in measuring HRQoL in COPD patients, and the VAS8 is particularly beneficial because of its ease of use.

Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMRglc) was measured before surgery and sequentially for 2–3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMRglc decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital cortices, as well as in the posterior hippocampal region, all of which also exhibit glucose hypometabolism in Alzheimer's disease. Remarkably, the degree of CMRglc decline in four of these regions significantly correlated with the severity of histologically determined damage in the rhinal cortex, strongly supporting the specificity of the observed metabolic effects. There were also differences between the metabolic pattern observed in the lesioned animals and that classically reported in Alzheimer's disease; for instance, the hypometabolism we found in the stratum has not been reported in early Alzheimer's disease, although this structure can be affected in late stages of the disease and has direct anatomical connections with the rhinal cortex. Nevertheless, this study shows for the first time that the temporoparietal and hippocampal hypometabolism found in Alzheimer's disease may partly result from neuroanatomical disconnection with the rhinal cortex. This, in turn, further strengthens the hypothesis that neuronal damage and dysfunction in the rhinal cortices play a major role in the expression of Alzheimer's disease.

A new fabrication process for nanoscale tungsten tip arrays was developed for scanning probe microscopy-based devices. It is suitable to make a huge array on a device chip and is potentially compatible with CMOS technology. In this study, tungsten was selected as a tip material because of its hardness and conductivity. The newly developed fabrication process mainly consists of several important techniques: a combination of optical lithography and electron beam (EB) lithography to reduce the total exposure time with high resolution and chromium/tungsten/chromium (Cr/W/Cr) sandwich deposition and etching in which the first chromium layer is used as a mask and a second one is used as an etch stop. A periodic array of dots in an EB resist with a spot diameter of less than 50 nm was obtained by a combination of optical lithography and EB lithography with a positive resist (polymethylmethacrylate) in which all processing conditions were optimized carefully. A thin and uniform chromium film, deposited by ion-beam sputtering, allowed the use of thin polymethylmethacrylate (PMMA) film which led to the high resolution. The conditions of dc magnetron sputtering were also optimized in order to deposit a densely packed and low-resistivity film. The resulting tungsten tip arrays had a cylindrical shape with diameters of less than 60 nm and heights of 300 nm.

Newland, Philip L. and Yasuhiro Kondoh. Dynamics of neurons controlling movements of a locust hind leg. III. Extensor tibiae motor neurons. J. Neurophysiol. 77: 3297–3310, 1997. Imposed movements of the apodeme of the femoral chordotonal organ (FeCO) of the locust hind leg elicit resistance reflexes in extensor and flexor tibiae motor neurons. The synaptic responses of the fast and slow extensor tibiae motor neurons (FETi and SETi, respectively) and the spike responses of SETi were analyzed with the use of the Wiener kernel white noise method to determine their response properties. The first-order Wiener kernels computed from soma recordings were essentially monophasic, or low passed, indicating that the motor neurons were primarily sensitive to the position of the tibia about the femorotibial joint. The responses of both extensor motor neurons had large nonlinear components. The second-order kernels of the synaptic responses of FETi and SETi had large on-diagonal peaks with two small off-diagonal valleys. That of SETi had an additional elongated valley on the diagonal, which was accompanied by two off-diagonal depolarizing peaks at a cutoff frequency of 58 Hz. These second-order components represent a half-wave rectification of the position-sensitive depolarizing response in FETi and SETi, and a delayed inhibitory input to SETi, indicating that both motor neurons were directionally sensitive. Model predictions of the responses of the motor neurons showed that the first-order (linear) characterization poorly predicted the actual responses of FETi and SETi to FeCO stimulation, whereas the addition of the second-order (nonlinear) term markedly improved the performance of the model. Simultaneous recordings from the soma and a neuropilar process of FETi showed that its synaptic responses to FeCO stimulation were phase delayed by about −30° at 20 Hz, and reduced in amplitude by 30–40% when recorded in the soma. Similar configurations of the first and second-order kernels indicated that the primary process of FETi acted as a low-pass filter. Cross-correlation between a white noise stimulus and a unitized spike discharge of SETi again produced well-defined first- and second-order kernels that showed that the SETi spike response was also dependent on positional inputs. An elongated negative valley on the diagonal, characteristic of the second-order kernel of the synaptic response in SETi, was absent in the kernel from the spike component, suggesting that information is lost in the spike production process. The functional significance of these results is discussed in relation to the behavior of the locust.

A surface-micromachined active probe device with built-in electrostatic actuator and on-chip CMOS circuits is described. The device has been fabricated on a silicon-on-insulator (SOI) substrate using a 0.6-/spl mu/m CMOS-based process containing four polysilicon layers and one metal layer, and its basic functionality has been verified experimentally. A 0.135-/spl mu/m-thick surface silicon layer of an SOI substrate was used to form cantilever beams. The very thin structures enable a probe to be turned on at a voltage as low as several volts. A stopper structure, used to avoid contact between a deflector electrode and its paired stator electrode, was formed with a small overlap area of approximately 0.05 /spl mu/m/sup 2/. The small overlap area results in a small adhesion force, approximately 70 nN. An n-p-n junction was exploited as an isolator in the probe. A p-n junction in a released beam had only a 5-pA leakage current at a 9-V reverse bias. In addition, it has been found that electrostatic charging is a major source causing unrestorable postrelease stiction.

Although health-related quality of life (HRQL) has recently been considered to be an important outcome in clinical trials of idiopathic pulmonary fibrosis (IPF), its relationship with survival is unknown.To determine the prognostic significance of HRQL scores in IPF assessed with the SGRQ.Eighty-seven consecutive patients with IPF, who had undergone evaluations and completed the St. George's Respiratory Questionnaire (SGRQ) at diagnosis were included in this study, as is the general practice. Cox proportional hazards analyses were performed to examine the relationship between HRQL scores and survival.The mean observation period was 44.2 +/- 29.6 mo, in the course of which 54 patients (62.0%) died. Univariate analysis revealed that the activity scores in the SGRQ(HR: 1.016, 95% CI: 1.004-1.029, P = 0.01) were significantly predictive of survival, although the symptoms, impacts, and total scores were not significantly related to mortality from all causes. However, multivariate analysis revealed that only the forced vital capacity percent predicted was a significant predictor of survival, and that the activity score in the SGRQwas not significantly related to mortality.There was no significant relationship between HRQL evaluated with the SGRQ and the subsequent mortality in IPF. The present negative result might suggest that HRQL is measuring an aspect other than one from physiological and functional impairment or disability.

A single-ray fast magnetosonic wave is used to drive current with strong absorption in a reversed field pinch, in conjunction with the usual ohmic current. Using a driven current smaller than the ohmic current, by an order of magnitude the converged field configurations approach Taylor's minimum energy state. The driven current profile is affected by the local beta value profile, which plays the role of broadening the driven current profile. Increasing the wave phase speed modifies the current density profile in the central region with a high driving efficiency so that it approaches the on-axis current peak profile, resulting in tearing mode stability. A sufficiently large poloidal driven current in the outer region reverses the toroidal field and would eliminate or reduce the need for dynamo action within the plasma. These favourable tendencies for both the approach to the minimum energy state and the field reversal become stronger as the wave phase speed decreases and the beta value increases. In conclusion, a proper selection of the wave power spectrum over the entire plasma region, which depends on the plasma beta value, is required to improve the plasma stability and the energy confinement time. Significant wave damping due to higher harmonic ion cyclotron resonances is observed for faster waves in higher beta plasmas

Although acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a well known clinical condition, predicting risk factors remain unknown. We evaluated the frequency, risk factors and impact on survival of AE-IPF.We retrospectively studied patients diagnosed with IPF based on the criteria of the ATS/ERS consensus statement and followed them for periods of more than 3 years except in dead cases. Initial characteristics including the level of dyspnoea, which was assessed with the modified Medical Research Council (MRC) scale, and decline of forced vital capacity (FVC) defined by at least 10% decline at 6 months, were evaluated as possible risk factors for AE.Seventy-four patients with IPF were studied. One-year, two-year, and three-year incidence of AE were 8.6%, 12.6%, and 23.9%, respectively. Multivariate analysis revealed that higher body mass index (BMI) [hazard ratio (HR), 1.20; 95% confidence interval (CI), 1.03-1.40], higher modified MRC scale [HR, 2.93; 95% CI, 1.46-5.85], and a decline in FVC at 6 mounths [HR, 0.97-2.60 (per mo); 95% CI, 1.01-7.45] were independent risk factors for AE-IPF. The causes of death were assessed to be AE in 20 of 57 expired patients. A stepwise multivariate Cox regression model evaluating AE-IPF, adjusted for %FVC and decline in FVC, demonstrated a statistically significant impact on overall survival [HR, 2.79; 95% CI, 1.59-4.88; p0.001].These data suggest that initial high modified MRC scale, high BMI, and decline in FVC at 6 months were significant independent risk factors for AE-IPF. AE was an independent prognostic factor in IPF.

The response properties and directional receptive fields of nonspiking local interneurons in the cercal system of the cockroach are described. Wind-evoked responses were recorded intracellularly, and then analyzed by means of the Wiener kernel method in which a Gaussian white noise signal was used as a stimulus. Cross-correlation between the response and the white noise signal produced first- (linear) and second-order (nonlinear) kernels that were used to define input-output characteristics of the interneurons. Three sets of interneurons were distinguished on the basis of kernel analysis. First, responses in interneurons 101, 107, 111, and 203 were characterized predominantly by a differentiating first-order kernel, which suggests a linear relationship to the stimulus. The amplitude and waveform of the kernel changed with the change in stimulus angle, indicating that these four cells are directionally sensitive. Second, responses in interneurons 102 and 103 were also directionally sensitive but highly nonlinear. The first-order kernel was biphasic, whereas the second-order kernel had an elongated depolarizing peak on the diagonal. The response dynamics were accounted for by a cascade of two filters, a linear band-pass filter and a static nonlinear filter, in which the nonlinearity is a signal compression (or a rectification). Third, responses in interneurons 104 and 201 consist largely of the second-order nonlinear component. The second-order kernel, which had an elongated depolarizing peak or a hyperpolarizing valley on the diagonal, did not show any directional preference. The second-order nonlinearity was dynamic, and could be modeled by a band-pass linear filter-static nonlinearity-low-pass linear filter cascade, where the static nonlinearity is a full-wave rectification. The band-pass filter would simply reflect the mechanical property of cercal hair sensilla, whereas the low-pass filter represents the transfer at synapses between the cercal afferents and the interneurons. The nonlinear response thus explains the difference in the directional sensitivity while the differentiating first-order kernel explains the velocity sensitivity of the interneurons. We show that 101 and 107 respond most preferentially to wind from the left versus right, whereas 102, 103, 111, and 203 respond to wind from the front versus rear. Thus, it is suggested that there are two subsystems responding maximally to wind displacement along two coordinate directions, one for the longitudinal direction and the other for the transverse direction. On the other hand, the full-wave-rectifier nonlinear interneurons are omnidirectional, and thus suggested to code simply the power of the wind displacement.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.

The purpose of this study was to reveal predictors for the long-term effects of pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) patients, in terms of health-related quality of life (HRQoL). We investigated the long-term effects of pulmonary rehabilitation in 53 COPD patients who had completed the outpatient program and could be evaluated continuously for 1 year. We also investigated factors related to long-term maintenance of HRQoL assessed by the St George's Respiratory Questionnaire (SGRQ). In the year following the program, the only items that retained a significant improvement compared with the pre-program levels were respiratory muscle strength and 6-min walking distance. Patients whose total SGRQ score showed improvements that were maintained above the minimal clinically important difference were placed in a maintained-improvements group (n = 18, 34.0%), and the others in a non-maintained group (n = 35, 66.0%). A comparison of the groups revealed that the maintained-improvements group had significantly lower forced vital capacity (FVC), inspiratory capacity (IC), and tidal volume (TV) at rest; higher PaCO(2); greater initial impairments in HRQoL; and more frequent attendance in a maintenance program. In a multiple logistic regression model, only PaCO(2) was identified as predictor for the maintenance of improvement in HRQoL over a long term. In conclusion, higher baseline PaCO(2) is predictor of maintained, long-term improvement in HRQoL after pulmonary rehabilitation. Frequent attendance in a maintenance program is another predictor.

Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMR(glc)) was measured before surgery and sequentially for 2-3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMR(glc) decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital cortices, as well as in the posterior hippocampal region, all of which also exhibit glucose hypometabolism in Alzheimer's disease. Remarkably, the degree of CMR(glc) decline in four of these regions significantly correlated with the severity of histologically determined damage in the rhinal cortex, strongly supporting the specificity of the observed metabolic effects. There were also differences between the metabolic pattern observed in the lesioned animals and that classically reported in Alzheimer's disease; for instance, the hypometabolism we found in the stratum has not been reported in early Alzheimer's disease, although this structure can be affected in late stages of the disease and has direct anatomical connections with the rhinal cortex. Nevertheless, this study shows for the first time that the temporoparietal and hippocampal hypometabolism found in Alzheimer's disease may partly result from neuroanatomical disconnection with the rhinal cortex. This, in turn, further strengthens the hypothesis that neuronal damage and dysfunction in the rhinal cortices play a major role in the expression of Alzheimer's disease.

A new microwave switch, the light-activated microwave photoconductive switch consisting of a heterostructure photoconductive switch (HPCS) with a flip-chip bonded vertical-cavity surface-emitting laser is reported. An insertion loss of 0.17 dB at a laser power of 15 mW and an isolation of 25 dB were obtained at 1 GHz. Excellent linearity was obtained with second and third order intercepts measured at 960 MHz of SOI=115 dBm and TOI=65 dBm at 960 MHz, respectively.

The accuracy of the scalar approximation technique in optical fiber analysis is investigated in detail. The scalar approximate solutions are compared numberically with the vector (rigorous) solutions for various linear refractive-index distributions, and several interesting features which are of practical importance are pointed out.

The anatomy and innervation of mesothoracic indirect flight muscles, dorsal longitudinal (DLM) and dorsoventral muscles (DVM) are described. The major DLMs depress the forewing, the major DYMs elevate it. The morphology of the motoneurones and unpaired median neurones (UM-neurone) innervating these muscles was investigated by back-filling with cobalt. The DLMs are innervated by eight paired motoneurones and one UM-neurone: one of these motoneurones has its cell body in the contralateral side of the mesothoracic ganglion, and the others have theirs in the ipsilateral side of the prothoracic ganglion. The DVMs are innervated by nine paired motoneurones and one UM-neurone, with their cell bodies in the ipsilateral and the median portion of the mesothoracic ganglion, respectively. All of the paired DLM and DVM motoneurones have many dendritic processes, mainly in the dorso-ipsilateral neuropile of the ganglia, but the DLM motoneurones also have processes in the contralateral neuropile. Each UM-neurone has its cell body in the postero-medial cortex of the mesothoracic ganglion, extending a single median neurite anteriorly to the dorsal neuropile where it bifurcates to form a right and left axon. The arrangement of the mesothoracic indirect flight motoneurones in different insect orders is discussed in terms of the neural organization of the flight system.

SummaryThe prognosis of patients with idiopathic pulmonary fibrosis (IPF) is generally considered to be poor. As the disease progresses, patients invariably become severely limited in their activities. Therefore, evaluating the health-related quality of life (HRQoL) in IPF patients is considered to be important. However, there have been few studies of this kind to date.We applied the St. George's Respiratory Questionnaire (SGRQ) to 41 consecutive IPF patients and examined various physiological variables to identify factors that were correlated with the HRQoL.Total lung capacity, transfer factor, arterial partial pressure of oxygen at rest, the lowest oxygen saturation during exercise test, and the baseline dyspnoea index (BDI) score were significantly correlated with the total SGRQ score. A similar tendency was observed in each component. Conversely, peak oxygen uptake, known as one of the important factors that determines HRQoL in chronic obstructive pulmonary disease (COPD), did not correlate with any SGRQ scores. In stepwise multiple regression analysis, the BDI score was selected as the only factor significantly contributing to the total SGRQ score.Dyspnoea was the most important factor determining HRQoL in IPF. The types of other variables that correlated with the HRQoL in IPF patients were different from those in COPD.